Induction of rat liver alkaline phosphatase: the mechanism of the serum elevation in bile duct obstruction

Abstract

Bile duct ligation in the rat leads to a rapid increase in hepatic and serum alkaline phosphatase activity. Within 12 hr after bile duct ligation, hepatic alkaline phosphatase has increased 7-fold and serum alkaline phosphatase activity 2k-fold. The elevation in the serum activity is completely due to an' increase in an isozyme that appears to originate in the liver. This serum isozyme and liver phosphatase, both partially purified by DEAE-cellulose column chromatography, have identical Michaelis constants, pH optima, and rates of heat denaturation. These isozymes migrate identically when subjected to electrophoresis on polyacrylamide gel, and their migration rates are equally slowed after neuraminidase digestion. The data suggest that the rise in hepatic alkaline phosphatase activity is dependent on de novo protein synthesis. Cycloheximide, in a dose that inhibited incorporation of leucine-14C into protein by 68%, inhibited the rise in liver phosphatase by 98% and that in serum by 80%. The rise in liver phosphatase activity could not be accounted for by simple retention of alkaline phosphatase that would normally appear in bile. The rise in liver activity after bile duct ligation was 240 times greater than the amount of phosphatase that normally appears in bile over a similar period of time. Cycloheximide had no effect on the bile duct ligation-induced changes in the serum and liver glutamic pyruvic transaminase.An abstract has been published in 1969 J. Clin. Invest. 48: 42a, and a preliminary report has appeared in

Primary structure of rat liver alkaline phosphatase deduced from its cDNA

“…Rat liver ALP, though its basal concentration is quite low, is easily inducible in response to various stimuli (Kaplan & Righetti, 1970;Pekarthy et al, 1972). In particular, a much higher concentration of ALP is induced in the liver by treatment of rat by bile-duct ligation in combination with colchicine injection (Ikehara et al, 1978;Oda & Ikehara, 1981).…”

Inhibition of serum alkaline phosphatase activity by phenylalanine and cholic acid.

“…Takata (1931) reported that liver alkaline phosphatase is sensitive to phenyalalnine and resistant to cholic acid inhibition. Kaplan and Righetti (1970) reported that in biliary tract obstruction there is a rise of hepatic alkaline phosphatase synthesis. The biliary tract obstruction or cholestasis occurs frequently in liver cirrhosis and this basic pathological process cann ot be different in its incidence among different blood types .…”

Biomarkers for Bone Tumors: Discovery from Genomics and Proteomics Studies and Their Challenges

“…Discovery of genomics as an indicator. However, the enzyme was previously reported to be high in patients with diseases of the liver, thus making it unsuitable for use as a bone tumor marker (5,6). Furthermore, this marker may be more useful for monitor ing progression of bone tumor but not as its diagnostic marker.…”